Details
Stereochemistry | ACHIRAL |
Molecular Formula | C24H23FN4O3 |
Molecular Weight | 434.4628 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
FC1=CC=C(CC2=NNC(=O)C3=C2C=CC=C3)C=C1C(=O)N4CCN(CC4)C(=O)C5CC5
InChI
InChIKey=FDLYAMZZIXQODN-UHFFFAOYSA-N
InChI=1S/C24H23FN4O3/c25-20-8-5-15(14-21-17-3-1-2-4-18(17)22(30)27-26-21)13-19(20)24(32)29-11-9-28(10-12-29)23(31)16-6-7-16/h1-5,8,13,16H,6-7,9-12,14H2,(H,27,30)
Molecular Formula | C24H23FN4O3 |
Molecular Weight | 434.4628 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Olaparib is an oral inhibitor of poly (ADP-ribose) polymerase enzymes, including PARP1, PARP2, and PARP3 which are involved in normal cellular homeostasis, such as DNA transcription, cell cycle regulation, and DNA repair. Olaparib has shown activity in ovarian and breast tumors with known BRCA mutations and was the first FDA approved drug in this class. Lynparza (olaparib) is indicated for treatment of gBRCA-mutated advanced ovarian cancer. Its use together with other chemotherapy medicines can lead to increased effects on the blood resulting in reduction in the numbers of white blood cells and platelets, and anaemia.
Originator
Approval Year
PubMed
Title | Date | PubMed |
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Tailored targeted therapy for all: a realistic and worthwhile objective? | 2009 |
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Are current drug development programmes realising the full potential of new agents? The scenario. | 2009 |
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Converting cancer mutations into therapeutic opportunities. | 2009 Sep |
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Recent advances in managing triple-negative breast cancers. | 2009 Sep 28 |
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Prevalence and predictors of loss of wild type BRCA1 in estrogen receptor positive and negative BRCA1-associated breast cancers. | 2010 |
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Triple-negative breast cancer. | 2010 |
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Chemotherapy resistance in metastatic breast cancer: the evolving role of ixabepilone. | 2010 |
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Present and future evolution of advanced breast cancer therapy. | 2010 |
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Emergence of rationally designed therapeutic strategies for breast cancer targeting DNA repair mechanisms. | 2010 |
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Estrogen receptor positive breast cancers in BRCA1 mutation carriers: clinical risk factors and pathologic features. | 2010 |
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Targeted therapy in ovarian cancer. | 2010 |
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Targeted therapies in epithelial ovarian cancer. | 2010 |
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A current review of targeted therapeutics for ovarian cancer. | 2010 |
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The Emerging Role of PARP Inhibitors in the Treatment of Epithelial Ovarian Cancer. | 2010 |
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Biology-driven cancer drug development: back to the future. | 2010 Apr 12 |
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BRCA mutations in the management of breast cancer: the state of the art. | 2010 Dec |
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Are current development programs realising the full potential of new agents? | 2010 Dec 20 |
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ATM deficiency sensitizes mantle cell lymphoma cells to poly(ADP-ribose) polymerase-1 inhibitors. | 2010 Feb |
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PARP inhibitors in BRCA1/BRCA2 germline mutation carriers with ovarian and breast cancer. | 2010 Feb 11 |
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Sensitivity and acquired resistance of BRCA1;p53-deficient mouse mammary tumors to the topoisomerase I inhibitor topotecan. | 2010 Feb 15 |
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Gateways to clinical trials. | 2010 Jan-Feb |
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[Treatment with oral agents for breast cancer]. | 2010 Jul |
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Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. | 2010 Jul 24 |
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Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. | 2010 Jul 24 |
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Sensitization to radiation and alkylating agents by inhibitors of poly(ADP-ribose) polymerase is enhanced in cells deficient in DNA double-strand break repair. | 2010 Jun |
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Society for biomolecular sciences - 16th annual conference & exhibition - advancing the science of drug discovery. | 2010 Jun |
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Poly(adp-ribose) polymerase inhibitors: a novel drug class with a promising future. | 2010 Mar-Apr |
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Multiple roles of BRIT1/MCPH1 in DNA damage response, DNA repair, and cancer suppression. | 2010 May |
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Poly(ADP)-ribose polymerase inhibition: frequent durable responses in BRCA carrier ovarian cancer correlating with platinum-free interval. | 2010 May 20 |
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Does race affect outcomes in triple negative breast cancer? | 2010 May 7 |
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Targeting poly(ADP-ribose) polymerase activity for cancer therapy. | 2010 Nov |
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The PARP inhibitor olaparib induces significant killing of ATM-deficient lymphoid tumor cells in vitro and in vivo. | 2010 Nov 25 |
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Central nervous system penetration and enhancement of temozolomide activity in childhood medulloblastoma models by poly(ADP-ribose) polymerase inhibitor AG-014699. | 2010 Nov 9 |
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Targeted therapies: PARP inhibitor olaparib is safe and effective in patients with BRCA1 and BRCA2 mutations. | 2010 Oct |
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Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombination. | 2010 Oct |
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Role for the mammalian Swi5-Sfr1 complex in DNA strand break repair through homologous recombination. | 2010 Oct 14 |
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Treatment options for patients with triple-negative breast cancer. | 2010 Oct 27 |
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Favorable response to doxorubicin combination chemotherapy does not yield good clinical outcome in patients with metastatic breast cancer with triple-negative phenotype. | 2010 Oct 5 |
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Gateways to clinical trials. | 2010 Sep |
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PARP inhibition: targeting the Achilles' heel of DNA repair to treat germline and sporadic ovarian cancers. | 2010 Sep |
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Checkpoint signaling, base excision repair, and PARP promote survival of colon cancer cells treated with 5-fluorodeoxyuridine but not 5-fluorouracil. | 2011 |
|
5-Benzamidoisoquinolin-1-ones and 5-(ω-carboxyalkyl)isoquinolin-1-ones as isoform-selective inhibitors of poly(ADP-ribose) polymerase 2 (PARP-2). | 2011 Apr 14 |
|
MSH3 mediates sensitization of colorectal cancer cells to cisplatin, oxaliplatin, and a poly(ADP-ribose) polymerase inhibitor. | 2011 Apr 8 |
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Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. | 2011 Jul |
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BAP1 loss defines a new class of renal cell carcinoma. | 2012 Jun 10 |
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Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors. | 2012 Nov 1 |
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Lessons learned from the fate of AstraZeneca's drug pipeline: a five-dimensional framework. | 2014 Jun |
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5-Fluorouracil-induced RNA stress engages a TRAIL-DISC-dependent apoptosis axis facilitated by p53. | 2015 Dec 22 |
|
DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. | 2015 Oct 29 |
Patents
Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Oct 21 20:30:34 UTC 2019
by
admin
on
Mon Oct 21 20:30:34 UTC 2019
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Record UNII |
WOH1JD9AR8
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Record Status |
Validated (UNII)
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Classification Tree | Code System | Code | ||
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NDF-RT |
N0000191623
Created by
admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
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EMA ASSESSMENT REPORTS |
LYNPARZA (AUTHORIZED: OVARIAN NEOPLASMS)
Created by
admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
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FDA ORPHAN DRUG |
417613
Created by
admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
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EU-Orphan Drug |
EU/3/07/501
Created by
admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
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FDA ORPHAN DRUG |
409213
Created by
admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
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WHO-ATC |
L01XX46
Created by
admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
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FDA ORPHAN DRUG |
655318
Created by
admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
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NCI_THESAURUS |
C62554
Created by
admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
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FDA ORPHAN DRUG |
419013
Created by
admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
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Code System | Code | Type | Description | ||
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SUB32234
Created by
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PRIMARY | |||
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M8185
Created by
admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
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PRIMARY | Merck Index | ||
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CHEMBL521686
Created by
admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
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PRIMARY | |||
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C71721
Created by
admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
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PRIMARY | |||
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8685
Created by
admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
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1597582
Created by
admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
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7519
Created by
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763113-22-0
Created by
admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
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23725625
Created by
admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
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DB09074
Created by
admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
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C531550
Created by
admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
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OLAPARIB
Created by
admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
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N0000191622
Created by
admin on Mon Oct 21 20:30:35 UTC 2019 , Edited by admin on Mon Oct 21 20:30:35 UTC 2019
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PRIMARY | Poly(ADP-Ribose) Polymerase Inhibitors [MoA] |
Related Record | Type | Details | ||
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METABOLIC ENZYME -> SUBSTRATE |
MAJOR
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TRANSPORTER -> SUBSTRATE | |||
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EXCRETED UNCHANGED |
FECAL
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TRANSPORTER -> INHIBITOR |
INHIBITOR
IC50
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TRANSPORTER -> INHIBITOR |
The clinical relevance of these findings is unknown.
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BINDER->LIGAND |
BINDING
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TARGET -> INHIBITOR |
DT40 cells cytotoxicity
BINDING
IC50
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TRANSPORTER -> INHIBITOR |
INHIBITOR
IC50
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TRANSPORTER -> INHIBITOR |
INHIBITOR
IC50
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TRANSPORTER -> INHIBITOR |
INHIBITOR
IC50
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EXCRETED UNCHANGED |
URINE
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TRANSPORTER -> INHIBITOR |
INHIBITOR
IC50
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METABOLIC ENZYME -> INHIBITOR |
Inhibitor at higher concentrations than are clinically achieved.
MINOR
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TRANSPORTER -> INHIBITOR |
INHIBITOR
IC50
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TRANSPORTER -> INHIBITOR |
INHIBITOR
IC50
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Volume of Distribution | PHARMACOKINETIC |
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Tmax | PHARMACOKINETIC |
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Biological Half-life | PHARMACOKINETIC |
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